# US 9,872,938 B2 · Methods, compositions and techniques for polydimethylsiloxane surface modifications

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- Number: US 9,872,938 B2
- Document ID: US9872938B2
- Status: Granted
- Kind: B2
- Application number: 15/162,328
- Filed: 2016-05-23
- Published: 2016-11-24
- Granted: 2018-01-23
- Earliest claimed: 2015-05-22
- Assignees: Orthobond, Inc.
- Applicants: Orthobond, Inc.
- Inventors: Randy Clevenger; Se-Ho Kim; Jordan Katz; Carlos Caicedo-Carvajal
- Web page: https://patentgrep.com/patent/US9872938B2

## CPC

- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- C08F 220/34: Esters containing nitrogen {, e.g. N,N-dimethylaminoethyl (meth)acrylate}
- C08G 77/42: Block-or graft-polymers containing polysiloxane sequences (polymerising aliphatic unsaturated monomers on to a polysiloxane C08F283/12)
- A61L 2300/208: Quaternary ammonium compounds
- A61L 2300/404: Biocides, antimicrobial agents, antiseptic agents
- A61L 2430/04: for mammary reconstruction
- C08F 2438/01: Atom Transfer Radical Polymerization [ATRP] or reverse ATRP
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- C08F: MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS

## Abstract

Disclosed are novel compositions and methods for making a polymer substrate and a ligand that includes a proximal portion with a photoactive compound bound to the polymer substrate, a terminal portion with an anti-infective/anti-microbial compound, and a reactive portion attaching the proximal portion and the terminal portion.

## Claims

### Claim 1

A composition comprising a polymer substrate, wherein the polymer substrate comprises a polysiloxane material, and a ligand covalently bonded to the polymer substrate, the ligand comprising
(i) a proximal portion based on a photoactive compound, the proximal portion covalently bonded to the polymer substrate,
(ii) a terminal portion comprising a covalently bonded anti-microbial compound, and
(iii) a reactive portion covalently attaching the proximal portion and the terminal portion.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the polysiloxane material is a polydimethyl siloxane.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the proximal portion consists of the following formula:
wherein A and B are each independently selected from a group consisting of a 5-membered aromatic, a 5-membered heteroaromatic, a 6-membered aromatic, and a 6-membered heteroaromatic;
Y is a moiety selected from a group consisting of hydrogen, hydroxyl, halogen, and optionally substituted alkyl; and
X is a moiety selected from a group consisting of O, S, SO—, —SO2—, —(CR1aR1b)—, —NR2—, —SO2NR2—, and —NR2SO2—, wherein R1a and R1b are independently selected from a group consisting of hydrogen, halogen, and alkyl and R2 is selected from a group consisting of hydrogen and alkyl.

### Claim 4 (depends on 3)

The composition of claim 3, wherein at least one of A or B is a phenyl moiety.

### Claim 5 (depends on 3)

The composition of claim 3, wherein both A and B are a phenyl moiety.

### Claim 6 (depends on 3, 4, 5)

The composition of any of claims 3 to 5, wherein Y is a hydroxyl group.

### Claim 7 (depends on 3, 4, 5)

The composition of any of claims 3 to 5, wherein X is O.

### Claim 8 (depends on 1, 2, 3)

The composition of any of claims 1 to 3, wherein the reactive portion comprises an optionally substituted alkane.

### Claim 9 (depends on 8)

The composition of claim 8, wherein the alkane consists of from about 1 to about 100 carbons.

### Claim 10 (depends on 8)

The composition of claim 8, wherein the alkane is substituted.

### Claim 11 (depends on 10)

The composition of claim 10, wherein the alkane is substituted with O.

### Claim 12 (depends on 9)

The composition of claim 9, wherein the alkane consists of from about 5 to about 15 carbons.

### Claim 13 (depends on 1, 2, 3)

The composition of any of claims 1 to 3, wherein the reactive portion comprises a polyethylene glycol.

### Claim 14 (depends on 1, 2, 3)

The composition of any of claims 1 to 3, wherein the terminal portion comprises a methacrylate moiety.

### Claim 15 (depends on 1, 2, 3)

The composition of any of claims 1 to 3, wherein the terminal portion is derived from 12-methacryloyloxydodecylpyridinium bromide.

### Claim 16 (depends on 1, 2, 3)

The composition of any of claims 1 to 3, wherein the ligand is selected from a group consisting of:
wherein, x, y and n are independently integers from 0 to 100.

### Claim 17 (depends on 1)

The composition of claim 1, wherein the polymer substrate is a medical device.

### Claim 18 (depends on 17)

The composition of claim 17, wherein the medical device is implantable.

### Claim 19 (depends on 1)

The composition of claim 1, wherein the polymer substrate is a breast implant.

### Claim 20 (depends on 1)

The composition of claim 1, wherein the polymer substrate is polydimethylsiloxane.

### Claim 21 (depends on 1)

The composition of claim 1, wherein the anti-microbial compound is a quaternary ammonium compound or a phosphonium compound.

### Claim 22 (depends on 1)

The composition of claim 1, wherein the photoactive compound is activated by UV light.

### Claim 23

A method of covalently bonding a ligand to a surface of a polymer substrate, the ligand comprising
(i) a proximal portion based on a photoactive compound, the proximal portion covalently bonded to the polymer substrate,
(ii) a terminal portion comprising a covalently bonded anti-microbial compound, and
(iii) a reactive portion covalently attaching the proximal portion and the terminal portion;
the method comprising:
applying a composition to a surface of the polymer substrate, the composition comprising a linker attached to a reactive portion;
applying photocatalytic ultraviolet light to the surface to attach the linker to the polymer substrate; and
attaching a terminal portion comprising an anti-microbial compound to the reactive portion using atom transfer radical polymerization to render the surface antimicrobial.

### Claim 24 (depends on 23)

The method of claim 23, wherein the polymer substrate comprises a polysiloxane material.

### Claim 25 (depends on 23)

The method of claim 23 wherein the composition is [4-[(11-undecyloxy-α-bromoisobutryl)-oxy]phenyl]phenyl methanone.

### Claim 26 (depends on 23, 24, 25)

The method of any of claims 23 to 25 comprising, applying the composition via spraying onto the surface.

### Claim 27 (depends on 23, 24, 25)

The method of any of claims 23 to 25 comprising, applying the composition via an applicator.

### Claim 28 (depends on 27)

The method of claim 27, wherein the applicator is a brush.

### Claim 29 (depends on 23)

The method of claim 23, wherein the wavelength of the ultraviolet light is about 500 nm or less.

### Claim 30 (depends on 23)

The method of claim 23, wherein the wavelength of the ultraviolet light is about 400 nm or less.

### Claim 31 (depends on 23)

The method of claim 23, wherein the wavelength of the ultraviolet light is about 370 nm or less.

### Claim 32 (depends on 23)

The method of claim 23, wherein the wavelength of the ultraviolet light is about 300 nm or less.

### Claim 33 (depends on 23)

The method of claim 23, wherein the wavelength of the ultraviolet light is about 254 nm or less.

### Claim 34 (depends on 23)

The method of claim 23, wherein intensity of the ultraviolet light is about 5 mW/cm2 or less.

### Claim 35 (depends on 23)

The method of claim 23, wherein intensity of the ultraviolet light is about 10 mW/cm2 or less.

### Claim 36 (depends on 23)

The method of claim 23, wherein intensity of the ultraviolet light is about 50 mW/cm2 or less.

### Claim 37 (depends on 23)

The method of claim 23, wherein intensity of the ultraviolet light is about 100 mW/cm2 or less.

### Claim 38 (depends on 23)

The method of claim 23, wherein intensity of the ultraviolet light is about 1000 mW/cm2 or less.

### Claim 39 (depends on 23)

The method of claim 23, wherein applying photocatalytic ultraviolet light to the surface comprises irradiating the surface for about 1 h or less.

### Claim 40 (depends on 23)

The method of claim 23, wherein applying photocatalytic ultraviolet light to the surface comprises irradiating the surface for about 2 h or less.

### Claim 41 (depends on 23)

The method of claim 23, wherein applying photocatalytic ultraviolet light to the surface comprises irradiating the surface for about 5 h or less.

### Claim 42 (depends on 23)

The method of claim 23, wherein applying photocatalytic ultraviolet light to the surface comprises irradiating the surface for about 10 h or less.

### Claim 43 (depends on 23)

The method of claim 23 wherein applying photocatalytic ultraviolet light to the surface comprises irradiating the surface for about 20 h or less.

### Claim 44 (depends on 23)

The method of claim 23, wherein applying photocatalytic ultraviolet light to the surface comprises irradiating the surface for about 30 h or less.

### Claim 45 (depends on 23)

The method of claim 23, wherein the polysiloxane material is a polydimethyl siloxane.

### Claim 46 (depends on 23)

The method of claim 23, wherein the linker consists of the following formula:
wherein A and B are each independently selected from a group consisting of a 5-membered aromatic, a 5-membered heteroaromatic, a 6-membered aromatic, and a 6-membered heteroaromatic;
Y is a moiety selected from a group consisting of hydrogen, hydroxyl, halogen, and optionally substituted alkyl; and
X is a moiety selected from a group consisting of O, S, SO—, —SO2—, —(CR1aR1b)—, —NR2—, —SO2NR2—, and —NR2SO2—, wherein R1a and R1b are independently selected from a group consisting of hydrogen, halogen, and alkyl, and R2 is selected from a group consisting of hydrogen and alkyl.

### Claim 47 (depends on 46)

The method of claim 46, wherein at least one of A or B is a phenyl moiety.

### Claim 48 (depends on 46)

The method of claim 46, wherein both A and B are a phenyl moiety.

### Claim 49 (depends on 46, 47, 48)

The method of any of claims 46 to 48, wherein Y is a hydroxyl group.

### Claim 50 (depends on 46, 47, 48)

The method of any of claims 46 to 48, wherein X is O.

### Claim 51 (depends on 46, 47, 48)

The method of any of claims 46 to 48, wherein the reactive portion comprises an optionally substituted alkane.

### Claim 52 (depends on 51)

The method of claim 51, wherein the alkane consists of from about 1 to about 100 carbons.

### Claim 53 (depends on 51)

The method of claim 51, wherein the alkane is substituted.

### Claim 54 (depends on 53)

The method of claim 53, wherein the alkane is substituted with O.

### Claim 55 (depends on 52)

The method of claim 52 wherein the alkane consists of from about 5 to about 15 carbons.

### Claim 56 (depends on 46, 47, 48)

The method of any of claims 46 to 48, wherein the reactive portion comprises a polyethylene glycol.

### Claim 57 (depends on 23, 24, 25, 47)

The method of any of claims 23 to 25 and 47, wherein the terminal portion comprises a methacrylate moiety.

### Claim 58 (depends on 23, 24, 25, 47)

The method of any of claims 23 to 25 and 47, wherein the terminal portion is derived from 12-methacryloyloxydodecylpyridinium bromide.

### Claim 59 (depends on 23)

The method of claim 23, wherein the surface rendered antimicrobial comprises a ligand selected from a group consisting of:
wherein, x, y and n are independently integers from 0 to 100.

### Claim 60 (depends on 23)

The method of claim 23, wherein the polymer substrate is a medical device.

### Claim 61 (depends on 60)

The method of claim 60, wherein the medical device is implantable.

### Claim 62 (depends on 23)

The method of claim 23, wherein the polymer substrate is a breast implant.

### Claim 63 (depends on 24)

The method of claim 24, wherein the polymer substrate comprises polydimethylsiloxane.

### Claim 64 (depends on 23)

The method of claim 23, wherein the anti-microbial compound is selected from a quaternary ammonium compound or a phosphonium compound.

### Claim 65 (depends on 1)

The composition of claim 1, wherein area density of the anti-microbial compound on the surface of the polymer substrate is about 1×1014 molecules/cm2 to about 1×1019 molecules/cm2.

### Claim 66 (depends on 65)

The composition of claim 65 wherein the area density of the anti-microbial compound on the surface of the polymer substrate is from about 1×1015 molecules/cm2 to about 1×1018 molecules/cm2.

### Claim 67 (depends on 23)

The method of claim 23, wherein area density of the anti-microbial compound on the surface of the polymer substrate is about 1×1014 molecules/cm2 to about 1×1019 molecules/cm2.

### Claim 68 (depends on 67)

The method of claim 67, wherein the area density of the anti-microbial compound on the surface of the polymer substrate is from about 1×1015 molecules/cm2 to about 1×1018 molecules/cm2.